Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass

Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on bone by increasing bone formation and reducing bone resorption, and thus has favorable effects in both aspects of bone volume regulation. In a phase 2 study, romosozumab increased areal BMD at the lumbar spine and total hip as measured by DXA compared with placebo, alendronate, and teriparatide in postmenopausal women with low bone mass. In additional analyses from this international, randomized study, we now describe the effect of romosozumab on lumbar spine and hip volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of participants receiving placebo, s.c. teriparatide (20 µg once daily), and s.c. romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar spine (mean of L₁ and L₂ entire vertebral bodies, excluding posterior processes) and hip. One year of treatment with romosozumab significantly increased integral vBMD and BMC at the lumbar spine and total hip from baseline, and compared with placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved significantly and similarly from baseline (p < 0.05) with both romosozumab (18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p < 0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for cortical vBMD (1.1% versus –0.9%, p = 0.12). Cortical BMC gains were larger with romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p < 0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to result in strength gains and support the continued clinical investigation of romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing phase 3 studies. © 2016 American Society for Bone and Mineral Research.     

Catch up in bone acquisition in young adult men with late normal puberty

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5‐year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual‐energy X‐ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R² aBMD 11.7%; BMC 4.3%), radius (R² aBMD 23.5%; BMC 22.3%), and lumbar spine (R² aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow‐up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years. © 2012 American Society for Bone and Mineral Research.     

Increased physical activity is associated with enhanced development of peak bone mass in men: a five-year longitudinal study

Data supporting physical activity guidelines to optimize bone development in men is sparse. Peak bone mass is believed to be important for the risk of osteoporosis later in life. The objective of this study was to determine if an increased amount of physical activity over a 5‐year period was associated with increased bone mineral content (BMC), areal (aBMD) and volumetric (vBMD) bone mineral density, and a favorable development of cortical bone size in young adult men. The original 1068 young men, initially enrolled in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study, were invited to participate in the longitudinal study, and a total of 833 men (78%), 24.1 ± 0.6 years of age, were included in the 5‐year follow‐up. A standardized self‐administered questionnaire was used to collect information about patterns of physical activity at both the baseline and 5‐year follow‐up visits. BMC and aBMD were measured using dual energy X‐ray absorptiometry, whereas vBMD and bone geometry were measured by peripheral quantitative computed tomography. Increased physical activity between the baseline and follow‐up visits was associated with a favorable development in BMC of the total body, and aBMD of the lumbar spine and total hip (p < 0.001), as well as with development of a larger cortex (cortical cross sectional area), and a denser trabecular bone of the tibia (p < 0.001). In conclusion, increased physical activity was related to an advantageous development of aBMD, trabecular vBMD and cortical bone size, indicating that exercise is important in optimizing peak bone mass in young men. © 2012 American Society for Bone and Mineral Research.     

Relation of vertebral deformities to bone density,structure, and strength

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2–3 (moderate/severe) deformities. aBMD was measured by dual‐energy X‐ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high‐resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load‐to‐strength ratio by finite‐element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2–3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age‐adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load‐to‐strength ratio (45‐degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making. © 2010 American Society for Bone and Mineral Research     

Odanacatib Treatment Affects Trabecular and Cortical Bone in the Femur of Postmenopausal Women: Results of a Two‐Year Placebo‐Controlled Trial

Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double‐blind, placebo‐controlled, 2‐year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant differential treatment effects (ODN‐PBO) for total hip integral (5.4%), trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months. There was no significant differential treatment effect on integral bone volume. Results for bone mineral content (BMC) closely matched those for vBMD for integral and trabecular compartments. However, with small but mostly significant differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to 1.9%), the percentage cortical BMC increases were numerically larger than those of vBMD. With a total hip BMC differential treatment effect (ODN‐PBO) of nearly 1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%, and 40% for the total, neck, trochanter, and intertrochanter subregions, respectively. In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular, and cortical vBMD and BMC at all femur regions relative to placebo when assessed by MIAF. Cortical volume and thickness increased significantly in all regions except the femoral neck. The increase in cortical volume and BMC paralleled the increase in cortical vBMD, demonstrating a consistent effect of ODN on cortical bone. Approximately one‐half of the absolute BMC gain occurred in cortical bone. © 2014 American Society for Bone and Mineral Research.     

Effects of skeletal size of the lumbar spine on areal bone density,volumetric bone density,and the diagnosis of osteoporosis in postmenopausal women in China

To understand the effects of skeletal size of the lumbar spine on areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and the diagnosis of osteoporosis in postmenopausal women, we measured the projected bone area, bone mineral content (BMC), aBMD, and vBMD at the anteroposterior and lateral lumbar spines in a population of 1081 postmenopausal Chinese women, 42 to 86 years of age. The results indicated that, at the anteroposterior and lateral lumbar spine, there were significant positive correlations between bone area and both BMC (r = 0.606; P = 0.000 and r = 0.610; P = 0.000) and aBMD (r = 0.270; P = 0.000 and r = 0.182; P = 0.000), but not vBMD (r = –0.055; P = 0.000 and r = 0.000; P = 0.929). When bone area at the anteroposterior spine changed by ±1 SD, the BMC, aBMD, and vBMD correspondingly changed by 28.2%, 10.1%, and 1.69% on the basis of their respective means. When a variation of ±1 SD was observed in bone area at the lateral spine, BMC and aBMD, correspondingly changed by 25.9% and 6.18% on the basis of their respective means, while vBMD indicated no change. Through comparisons among large-, intermediate-, and small-bone area groups, significant differences were found in the means of subjects heights, weights, BMC, and vBMD at the anteroposterior and lateral lumbar spines, as well as in the detection rates of osteoporosis by aBMD (P = 0.000). Detection rates of osteoporosis by aBMD at the anteroposterior spine and by aBMD at the lateral spine, and by vBMD were 44.1%, 55.5%, and 49.7%, respectively, in the total population; 31.4%, 41.7%, and 53.7%, respectively, in the large-bone area group; 43.3%, 55.9%, and 50.5%, respectively, in the intermediate-bone area group; and 61.7%, 70.0%, and 42.5%, respectively, in the small-bone area group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing skeletal size and aBMD of the lumbar spine were height and weight. Therefore, in menopausal women of the same ethnic group and age, the skeletal size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e., the larger the spinal size, the greater the aBMD and the lower the osteoporosis detection rate, while, conversely, the smaller the skeletal size, the smaller the aBMD and the higher the osteoporosis detection rate. When we use aBMD of the lumbar spine to diagnose osteoporosis in a population with different body sizes, we need to take this body size difference into account. When we use vBMD to diagnose osteoporosis, the effect of body size on BMD will diminish.     

Bone Density,Microstructure and Strength in Obese and Normal Weight Men and Women in Younger and Older Adulthood

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site‐specific differences in BMD, bone structure, or bone strength between obese and normal‐weight adults. We studied 100 individually‐matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m²) and obese (BMI >30 kg/m²) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual‐energy X‐ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high‐resolution peripheral QCT (HR‐pQCT) and micro–finite element analysis. Serum type 1 procollagen N‐terminal peptide (P1NP) and collagen type 1 C‐telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR‐pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age‐related bone loss and may increase peak bone mass. © 2014 American Society for Bone and Mineral Research.     

Longitudinal Change in Bone Density,Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS)

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Vertebral Size,Bone Density,and Strength in Men and Women Matched for Age and Areal Spine BMD

To explore the possible mechanisms underlying sex‐specific differences in skeletal fragility that may be obscured by two‐dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)‐based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross‐sectional area (CSA, cm²), trabecular volumetric BMD (Tb.vBMD, g/cm³), integral volumetric BMD (Int.vBMD, g/cm³), estimated vertebral compressive loading and strength (Newtons) at L₃, the factor‐of‐risk (load‐to‐strength ratio), and vertebral fracture prevalence. We identified 981 male‐female pairs (1:1 matching) matched on age (± 1 year) and QCT‐derived aBMD of L₃ (± 1%), with an average age of 51 years (range 34 to 81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower Int.vBMD (–8%) and Tb.vBMD (–9%), 10% greater vertebral compressive strength, 24% greater vertebral compressive loading, and 12% greater factor‐of‐risk than women (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After adjusting for height and weight, the differences in CSA and volumetric bone mineral density (vBMD) between men and women were attenuated but remained significant, whereas compressive strength was no longer different. In conclusion, vertebral size, morphology, and density differ significantly between men and women matched for age and spine aBMD, suggesting that men and women attain the same aBMD by different mechanisms. These results provide novel information regarding sex‐specific differences in mechanisms that underlie vertebral fragility. © 2014 American Society for Bone and Mineral Research.     

Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high bone mineral density (BMD) despite conventional treatment with calcium supplements and active vitamin D analogues. To assess effects of PTH substitution therapy on 3‐dimensional bone structure, we randomized 62 patients with hypoPT into 24 weeks of treatment with either PTH(1‐84) 100 µg/day subcutaneously or similar placebo as an add‐on therapy. Micro‐computed tomography was performed on 44 iliac crest bone biopsies (23 on PTH treatment) obtained after 24 weeks of treatment. Compared with placebo, PTH caused a 27% lower trabecular thickness (p < 0.01) and 4% lower trabecular bone tissue density (p < 0.01), whereas connectivity density was 34% higher (p < 0.05). Trabecular tunneling was evident in 11 (48%) of the biopsies from the PTH group. Patients with tunneling had significantly higher levels of biochemical markers of bone resorption and formation. At cortical bone, number of Haversian canals per area was 139% higher (p = 0.01) in the PTH group, causing a tendency toward an increased cortical porosity (p = 0.09). At different subregions of the hip, areal BMD (aBMD) and volumetric BMD (vBMD), as assessed by dual‐energy X‐ray absorptiometry (DXA) and quantitative computed tomography (QCT), decreased significantly by 1% to 4% in the PTH group. However, at the lumbar spine, aBMD decreased by 1.8% (p < 0.05), whereas vBMD increased by 12.8% (p = 0.02) in the PTH compared with the placebo group. © 2012 American Society for Bone and Mineral Research.     

Interaction between playing golf and HRT on vertebral bone properties in post-menopausal women measured by QCT

Summary We investigated the effect of playing regular golf and HRT on lumbar and thoracic vertebral bone parameters (measured by QCT) in 72 post-menopausal women. The main finding of this study was that there was positive interaction between golf and HRT on vertebral body CSA and BMC at the thoracic 12 and lumbar 2 vertebra but not the third and seventh thoracic vertebras. Introduction Identifying specific exercises that load the spine sufficiently to be osteogenic is an important component of primary osteoporosis prevention. The aim of this study was to determine if in postmenopausal women regular participation in golf resulted in greater paravertebral muscle mass and improved vertebral bone strength. Methods Forty-seven postmenopausal women who played golf regularly were compared to 25 controls. Bone parameters at the mid-vertebral body were determined by QCT at spinal levels T3, T7, T12 and L2 (cross-sectional area (CSA), total volumetric BMD (vBMD), trabecular vBMD of the central 50% of total CSA, BMC and cortical rim thickness). At T7 and L2, CSA of trunk muscles was determined. Results There was a positive interaction between golf and HRT for vertebral CSA and BMC at T12 and L2, but not at T3 or T7 (p ranging < 0.02 to 0.07). Current HRT use was associated with a 10–15% greater total and trabecular vBMD at all measured vertebral levels. Paravertebral muscle CSA did not differ between groups. Vertebral CSA was the bone parameter significantly related to muscle CSA. Conclusion These findings provide preliminary evidence that playing golf may improve lower spine bone strength in postmenopausal women who are using HRT.     

女性年龄相关的腰椎骨量与骨骼大小的关系及对诊断骨质疏松的影响

目的探讨腰椎骨量(面积骨密度和体积骨密度)与年龄和骨骼骨面积(BA)大小之间的关系,及腰椎骨骼大小对评价骨量和诊断骨质疏松(OP)的影响。方法采用QDR-4500A型扇形束双能X线吸收法骨密度仪,测量5585例年龄5～96岁的女性正位腰椎BA、骨矿含量(BMC)、面积骨密度(aBMD)及估算体积骨密度(vBMD)。结果腰椎aBMD和vBMD的峰值BMD(x珋±s)分别为0.9884±0.1064g/cm2和0.1310±0.0128g/cm3。在所有年龄阶段aBMD随年龄的变化率显著大于vBMD。腰椎BA与BMC、aBMD和vBMD均呈显著正相关,其中BA与BMC的相关系数最大(r=0.706,P=0.000),与aBMD的相关系数次之(r=0.394,P=0.000),与vBMD的相关系数最小(r=0.141,P=0.000)。年龄≥40岁(平均52.7±9.58岁)的受试者(n=4012)腰椎BA按四分位数分成Q1、Q2、Q3和Q4组,4个组之间的BA、BMC和aBMD的平均值均有显著性差异。采用aBMD诊断OP,4个组的OP检出率分别为Q1=33.6%、Q2=17.9%、Q3=13.3%和Q4=8.39%,呈显著性梯次降低;与总体组比较,Q1组的患病风险增加126%,Q2、Q3和Q4组的患病风险分别降低3%、31%和59%。采用vBMD诊断OP,4个组的OP检出率分别为Q1=27.4%、Q2=18.3%、Q3=15.9%和Q4=14.0%,其梯次差异显著低于aBMD;与总体组比较,Q1组的患病风险增加62%,Q2、Q3和Q4组的患病风险分别降低4%、19%和30%。Q1组aBMD的OP检出率显著高于vBMD,Q4组aBMD的OP检出率显著低于vBMD。在椎体最小的Q1组,aBMD(OR=2.26)的患病风险比vBMD(OR=1.62)大约高64%,在椎体最大的Q4组,aBMD(OR=0.41)的患病风险比vBMD(OR=0.70)大约低29%。结论该研究揭示腰椎vBMD并不能完全消除骨骼大小对评价骨量和诊断OP的影响。在腰椎椎体较小的受试者,aBMD诊断OP的敏感性高于vBMD;在椎体较大的受试者,vBMD诊断OP的敏感性则高于aBMD。     

T-Score as an Indicator of Fracture Risk During Treatment With Romosozumab or Alendronate in the ARCH Trial

In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) clinical trial (NCT01631214), 1 year of romosozumab followed by alendronate reduced the risk of vertebral and nonvertebral fractures compared to alendronate alone in women with prevalent fracture. We performed post hoc analyses of data from patients in ARCH (romosozumab, n = 1739; alendronate, n = 1726) who had a baseline BMD measurement and received at least one open-label alendronate dose. We evaluated 1-year mean BMD and corresponding T-score changes; proportions of patients achieving T-scores > −2.5 at the total hip (TH), femoral neck (FN), and lumbar spine (LS); and group differences in fracture rates after 12 months, while all participants were on alendronate. Subsequently, we investigated the relationship between T-scores achieved at the TH, FN, and LS at 12 months and subsequent fracture incidence. At 1 year, mean change from baseline in TH BMD was 6.3% (T-score change 0.31) with romosozumab versus 2.9% (T-score change 0.15) with alendronate (p < .001). The proportion of patients with TH T-score > −2.5 increased from 34% at baseline to 55% after 1 year of romosozumab and from 32% at baseline to 44% after 1 year of alendronate. Compared with patients receiving alendronate in year 1, those receiving romosozumab had a 75% reduction in new or worsening vertebral fracture (p < .001) in year 2, and a 19% reduction in nonvertebral fracture (p = .120) and 40% reduction in hip fracture (p = .041) during the open-label period. TH and FN T-scores achieved at month 12 were associated with subsequent nonvertebral and vertebral fracture rates and the relationships were independent of treatment received. LS T-score at 12 months was associated with vertebral but not nonvertebral fracture risk. We conclude that 1 year of romosozumab leads to larger BMD gains versus alendronate, and that the T-score achieved with either therapy is related to subsequent fracture risk. These data support the use of T-score as a therapeutic target for patients with osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Correlates of bone microarchitectural parameters and serum sclerostin levels in men: The STRAMBO study

Sclerostin is predominantly expressed by osteocytes. Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by dual‐energy X‐ray absorptiometry (DXA) and bone microarchitecture assessed by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in small studies. We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR‐pQCT in 1134 men aged 20 to 87 years using multivariable models adjusted for confounders (age, body size, lifestyle, comorbidities, hormones regulating bone metabolism, muscle mass and strength). The apparent age‐related increase in serum sclerostin levels was faster before the age of 63 years than afterward (0.43 SD versus 0.20 SD per decade). In 446 men aged ≤63 years, aBMD (spine, hip, whole body), trabecular volumetric BMD (Tb.vBMD), and trabecular number (Tb.N) at the distal radius and tibia were higher in the highest sclerostin quartile versus the three lower quartiles combined. After adjustment for aBMD, men in the highest sclerostin quartile had higher Tb.vBMD (mainly in the central compartment) and Tb.N at both skeletal sites (p < 0.05 to 0.001). In 688 men aged >63 years, aBMD was positively associated with serum sclerostin levels at all skeletal sites. Cortical vBMD (Ct.vBMD) and cortical thickness (Ct.Th) were lower in the first sclerostin quartile versus the three higher quartiles combined. Tb.vBMD increased across the sclerostin quartiles, and was associated with lower Tb.N and more heterogeneous trabecular distribution (higher Tb.Sp.SD) in men in the lowest sclerostin quartile. After adjustment for aBMD, men in the lowest sclerostin quartile had lower Tb.vBMD and Tb.N, but higher Tb.Sp.SD (p < 0.05 to 0.001) at both the skeletal sites. In conclusion, serum sclerostin levels in men are strongly positively associated with better bone microarchitectural parameters, mainly trabecular architecture, regardless of the potential confounders.     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research     

Bone mineral content and density of the lumbar spine of infants and toddlers: Influence of age,sex, race,growth, and human milk feeding

Little is known about factors that affect bone mass and density of infants and toddlers and the means to assess their bone health owing to challenges in studying this population. The objectives of this study were to describe age, sex, race, growth, and human milk feeding effects on bone mineral content (BMC) and areal density (aBMD) of the lumbar spine, and determine precision of BMC and aBMD measurements. We conducted a cross‐sectional study of 307 healthy participants (63 black), ages 1 to 36 months. BMC and aBMD of the lumbar spine were measured by dual‐energy X‐ray absorptiometry. Duplicate scans were obtained on 76 participants for precision determination. Age‐specific Z‐scores for aBMD, weight, and length (BMDZ, WAZ, LAZ) were calculated. Information on human milk feeding duration was ascertained by questionnaire. Between ages 1 and 36 months, lumbar spine BMC increased about fivefold and aBMD increased twofold (p < 0.0001). BMC was greater (5.8%) in males than in females (p = 0.001), but there was no difference in aBMD (p = 0.37). There was no difference in BMC or aBMD between whites and blacks (p ≥ 0.16). WAZ and LAZ were positively associated with BMDZ (r = 0.34 and 0.24, p < 0.001). Duration of human milk feeding was negatively associated with BMDZ in infants <12 months of age (r = ?0.42, p < 0.001). Precision of BMC and aBMD measurements was good, 2.20% and 1.84%, respectively. Dramatic increases in BMC and aBMD of the lumbar spine occur in the first 36 months of life. We provide age‐specific values for aBMD of healthy infants and toddlers that can be used to evaluate bone deficits. Future studies are needed to identify the age when sex and race differences in aBMD occur, and how best to account for delayed or accelerated growth in the context of bone health assessment of infants and toddlers. © 2013 American Society for Bone and Mineral Research     

Differences in skeletal microarchitecture and strength in African‐American and white women

African‐American women have a lower risk of fracture than white women, and this difference is only partially explained by differences in dual‐energy X‐ray absorptiometry (DXA) areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro–finite element analysis (µFEA) in African‐American (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation (SWAN). African‐American women had larger and denser bones than whites, with greater total area, aBMD, and total volumetric BMD (vBMD) at the radius and tibia metaphysis (p < 0.05 for all). African‐Americans had greater trabecular vBMD at the radius, but higher cortical vBMD at the tibia. Cortical microarchitecture tended to show the most pronounced racial differences, with higher cortical area, thickness, and volumes in African‐Americans at both skeletal sites (p < 0.05 for all), and lower cortical porosity in African‐Americans at the tibia (p < 0.05). African‐American women also had greater estimated bone stiffness and failure load at both the radius and tibia. Differences in skeletal microarchitecture and estimated stiffness and failure load persisted even after adjustment for DXA aBMD. The densitometric and microarchitectural predictors of failure load at the radius and tibia were the same in African‐American and white women. In conclusion, differences in bone microarchitecture and density contribute to greater estimated bone strength in African‐Americans and probably explain, at least in part, the lower fracture risk of African‐American women. © 2013 American Society for Bone and Mineral Research.     

Relation of adrenal-derived steroids with bone maturation,mineral density and geometry in healthy prepubertal and early pubertal boys

BackgroundLittle is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys.ObjectiveTo study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys.Methods98 healthy prepubertal and early pubertal boys (aged 6–14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand.ResultsAdrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD).ConclusionIn healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.     

Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes

Type 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long-standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m²; 5-year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82–7.40]) and 77 nondiabetic controls. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross-linked C-telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: −0.14 [−0.24, −0.05], p < 0.01) and lower cortical vBMD (−28.66 [−54.38, −2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long-standing, well-controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight.

We measured cortical and trabecular bone loss using QCT of the spine and hip in 14 crewmembers making 4- to 6-month flights on the International Space Station. There was no compartment-specific loss of bone in the spine. Cortical bone mineral loss in the hip occurred primarily by endocortical thinning. INTRODUCTION: In an earlier study, areal BMD (aBMD) measurements by DXA showed that cosmonauts making flights of 4- to 12-month duration on the Soviet/Russian MIR spacecraft lost bone at an average rate of 1%/month from the spine and 1.5%/month from the hip. However, because DXA measurements represent the sum of the cortical and trabecular compartments, there is no direct information on how these bone envelopes are affected by spaceflight. MATERIALS AND METHODS: To address this, we performed a study of crewmembers (13 males and 1 female; age range, 40-55 years) on long-duration missions (4-6 months) on the International Space Station (ISS). We used DXA to obtain aBMD of the hip and spine and volumetric QCT (vQCT) to assess integral, cortical, and trabecular volumetric BMD (vBMD) in the hip and spine. In the heel, DXA was used to measure aBMD, and quantitative ultrasound (QUS) was used to measure speed of sound (SOS) and broadband ultrasound attenuation (BUA). RESULTS AND CONCLUSIONS: aBMD was lost at rates of 0.9%/month at the spine (p < 0.001) and 1.4-1.5%/month at the hip (p < 0.001). Spinal integral vBMD was lost at a rate of 0.9%/month (p < 0.001), and trabecular vBMD was lost at 0.7%/month (p < 0.05). In contrast to earlier reports, these changes were generalized across the vertebrae and not focused in the posterior elements. In the hip, integral, cortical, and trabecular vBMD was lost at rates of 1.2-1.5%/month (p < 0.0001), 0.4-0.5%/month (p < 0.01), and 2.2-2.7%/month (p < 0.001), respectively. The cortical bone loss in the hip occurred primarily by cortical thinning. Calcaneal aBMD measurements by DXA showed smaller mean losses (0.4%/month) than hip or spine measurements, with SOS and BUA showing no change. In summary, our results show that ISS crewmembers, on average, experience substantial loss of both trabecular and cortical bone in the hip and somewhat smaller losses in the spine. These results do not support the use of calcaneal aBMD or QUS measurements as surrogate measures to estimate changes in the central skeleton.